In vitro method for predicting the evolutionary response of a pr

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving virus or bacteriophage

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435 6, 435 23, 4351721, 435 691, C12Q 168, C12Q 170, C12Q 137, C12Q 1548

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active

057668426

ABSTRACT:
A method for identifying, in vitro, distinct, drug-resistant, biologically-active mutants of a protein that may emerge in vivo in response to a drug targeted against the protein is disclosed. The method involves preparing, by heterologous expression of a library of nucleotide sequences, a complete library of mutant proteins accessible in a single generation. The mutant proteins from the library that are drug resistant are identified. When all the first generation mutants have been identified in the above manner, a combination of drugs can be identified that will block the development of resistance. The same technique allows evaluation of the ultimate clinical efficacy of a drug targeted against the protein by comparing the number of resistant first generation mutants. A preferred protein is an HIV protease.

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